The importance of C4A null genes in Norwegian patients with systemic lupus erythematosus.

C4A null genes were determined by RFLP (Taq I) and SSO-probing on PCR-amplified C4-DNA in 51 Scandinavian patients with systemic lupus erythematosus (SLE) and 124 controls. Associations of the alleles DRB10301, DQA10501, DQB10201 had previously been found in this SLE group, as well as increased frequency of HLA-DRB1 and -DQ homozygosity. The frequency of the allele C4AQ0 was increased among the patients (RR = 2.3, P = 0.0172). The SSO-probing revealed additional cases of C4AQ0 homozygotes among the controls, leading to diverging RR values for C4AQ0 homozygotes depending on the technique used. The RFLP method gave an RR of 9.7 (P = 0.0028), while the SSO-probing resulted in an RR of 4.8 (P = 0.0153), demonstrating that unprecise characterization of C4AQ0 in a relatively small material has great effect on the calculated RR. Multiple 2 x 2 tests were performed in an attempt to detect the strongest association of the alleles DRB10301, DQA10501 and C4AQ0 (in linkage disequilibrium). These comparisons showed a trend towards stronger association for DAQ10501 and DRB10301 than for C4AQ0, and no interaction between the HLA alleles and the allele C4AQ0. This may suggest that HLA class II molecules themselves and/or an unknown susceptibility gene located near the DQA1 and DRB1 loci are involved in the pathogenesis of SLE.